Hyperthermia is a cancer treatment in which tumors are elevated to cytotoxic temperatures (41- 45 oC) in order to aid in their control. A noninvasive method for volumetrically determining temperature distribution during treatment would greatly enhance the ability to uniformly heat tumors at therapeutic levels. Our long-term goal is to produce three-dimensional temperature maps in soft tissue, noninvasively, conveniently, and at low cost, with 0.5 oC accuracy and 1 cm3 resolution. Ultrasound is an attractive modality for this purpose. Changes in speed of sound, attenuation, and the location of echoes have been explored by others, but as yet not reduced to clinical practice. Here we plan to investigate changes in ultrasonic backscattered energy with temperature to provide a foundation for judging the accuracy and spatial resolution of this approach. In our preliminary work we developed an analytic model for the change in backscattered energy with temperature from tissue inhomogeneities in the form of small (subwavelength) scatterers. Our predicted changes in backscattered energy were matched by in vitro measurements in tissue samples. The ability to use our approach to estimate temperatures is nonetheless a high-risk proposition, however, because questions still exist with regard to the ability: 1) to track scatterers both in vitro and in vivo, and 2) to calibrate the temperature dependence of the energy received from these scatterers. To answer some of these questions, we plan to study a variety of tissue samples in vitro, over the 37 to 50 oC temperature range. Specifically, we intend: 1) to measure and model the change in backscattered ultrasonic energy from individual scatterers, 2) to track the position of individual scatterers with thermal expansion and changes in speed of sound, and 3) to estimate temperature over small volumes by using the backscatter properties of all the resolvable scatterers in the volume of interest. If changes in backscattered energy can used to estimate temperature, the benefits could be important for hyperthermia, other thermal therapies, and ultrasonic imaging in general. Because our approach exploits the inhomogeneities present in tissue, we believe that if it is successful in vitro; it holds promise for in vivo application.